癌癥研究人員可以測定腫瘤細(xì)胞基因組的序列,，掃描其異常的基因活性,，剖析其突變的蛋白質(zhì)和研究它們在實驗室培養(yǎng)皿中的生長，但研究者一直無法跟蹤細(xì)胞形成腫瘤的過程?，F(xiàn)在三個獨(dú)立研究小組在小鼠體內(nèi)做到了這一點(diǎn),。他們的研究結(jié)果支持這樣的觀點(diǎn)：一小部分細(xì)胞驅(qū)動腫瘤的生長，而想要治愈癌癥可能需要將這些所謂腫瘤干細(xì)胞清除,。
目前還無法確認(rèn),，這些從腦瘤，腸癌和皮膚癌研究的結(jié)論是否適用于其他類型腫瘤,，但是得克薩斯大學(xué)西南醫(yī)學(xué)中心的路易斯·帕拉達(dá)認(rèn)為,，如果它們適用于其他腫瘤，"將深刻地改變目前的化療療效評價和臨床療法的制定標(biāo)準(zhǔn)",。 不僅是看某種療法是否縮小腫瘤,，研究人員將更關(guān)注是否殺死了正確的細(xì)胞。
帕拉達(dá)和他的同事們想檢測是否特異性標(biāo)識健康成人神經(jīng)干細(xì)胞的一個遺傳標(biāo)記,，也可標(biāo)識神經(jīng)母細(xì)胞瘤中的癌癥干細(xì)胞,。他們發(fā)現(xiàn)，所有神經(jīng)母細(xì)胞瘤樣本中至少有幾個標(biāo)記細(xì)胞 - 大概是干細(xì)胞,。未標(biāo)記細(xì)胞可被標(biāo)準(zhǔn)化療殺死,，但腫瘤可迅速恢復(fù)。進(jìn)一步的實驗表明,，未標(biāo)記細(xì)胞起源于標(biāo)記的細(xì)胞祖先,。當(dāng)研究者把化療與抑制標(biāo)記細(xì)胞的遺傳手段相結(jié)合進(jìn)行治療時，帕拉達(dá)說,，腫瘤顯著縮小到"殘留遺跡"的水平,。
在另一項研究中，荷蘭烏得勒支Hubrecht研究所的干細(xì)胞生物學(xué)家們把注意力瞄著了腸道。利用藥物驅(qū)動的熒光素標(biāo)志物表達(dá)系統(tǒng),，他們在小鼠體內(nèi)證實,，多種不同類型的腫瘤細(xì)胞，其實是來源于同一干細(xì)胞的,。而且,，這些干細(xì)胞是腫瘤發(fā)展的驅(qū)動力。
對皮膚癌的研究,，Blanpain和他的小組標(biāo)記單個腫瘤細(xì)胞，而不是特異地標(biāo)記干細(xì)胞,。他們發(fā)現(xiàn),，細(xì)胞表現(xiàn)出兩種不同的分工模式：它們要么在慢慢耗盡前分裂出少數(shù)細(xì)胞，或者產(chǎn)生許多細(xì)胞,。這再次證實,，一類獨(dú)特的細(xì)胞亞群是腫瘤生長的驅(qū)動力。
研究者說,，下一步的研究計劃將是,，搞清楚這些實驗所跟蹤的細(xì)胞如何與通過多年移植實驗所確定的，假定的癌癥干細(xì)胞相聯(lián)系的,。研究人員已經(jīng)緊鑼密鼓地在尋找殺死這些細(xì)胞的方法;現(xiàn)在他們有更多的工具來測試這樣的策略是否會奏效,。（生物谷bioon.com）
編譯自：Cancer stem cells tracked
doi:10.1038/nature11344
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PMID:
Defining the mode of tumour growth by clonal analysis
Gregory Driessens,Benjamin Beck,Amélie Caauwe,Benjamin D. Simons& Cédric Blanpain
Recent studies using the isolation of a subpopulation of tumour cells followed by their transplantation into immunodeficient mice provide evidence that certain tumours1, 2, including squamous skin tumours3, 4, 5, contain cells with high clonogenic potential that have been referred to as cancer stem cells (CSCs). Until now, CSC properties have only been investigated by transplantation assays, and their existence in unperturbed tumour growth is unproven. Here we make use of clonal analysis of squamous skin tumours using genetic lineage tracing to unravel the mode of tumour growth in vivo in its native environment. To this end, we used a genetic labelling strategy that allows individual tumour cells to be marked and traced over time at different stages of tumour progression. Surprisingly, we found that the majority of labelled tumour cells in benign papilloma have only limited proliferative potential, whereas a fraction has the capacity to persist long term, giving rise to progeny that occupy a significant part of the tumour. As well as confirming the presence of two distinct proliferative cell compartments within the papilloma, mirroring the composition, hierarchy and fate behaviour of normal tissue, quantitative analysis of clonal fate data indicates that the more persistent population has stem-cell-like characteristics and cycles twice per day, whereas the second represents a slower cycling transient population that gives rise to terminally differentiated tumour cells. Such behaviour is shown to be consistent with double-labelling experiments and detailed clonal fate characteristics. By contrast, measurements of clone size and proliferative potential in invasive squamous cell carcinoma show a different pattern of behaviour, consistent with geometric expansion of a single CSC population with limited potential for terminal differentiation. This study presents the first experimental evidence for the existence of CSCs during unperturbed solid tumour growth.
